Drive mechanism for a delivery device

ABSTRACT

A drive mechanism for a delivery device is presented. The drive mechanism comprises a housing ( 24 ) and a piston rod ( 6 ) having a longitudinal axis (x) and a piston rod feature ( 17 ). The drive mechanism further comprises a drive member ( 1 ) being movable with respect to the housing ( 24 ). The drive member ( 1 ) comprises a drive feature ( 15 ). The drive feature ( 15 ) is selectively engageable with the piston rod feature ( 17 ) by the radial displacement of the drive member ( 1 ) with respect to the piston rod ( 6 ). When the drive member ( 1 ) is in the first position, the drive member ( 1 ) is disengaged from the piston rod ( 6 ), and when the drive member ( 1 ) is in the second position, the drive feature ( 15 ) is engaged with the piston rod feature ( 17 ). When the drive member ( 1 ) moves distally with respect to the housing ( 24 ), said distal movement is transferred to the piston rod ( 6 ) such that the piston rod ( 6 ) moves distally with respect to the housing ( 24 ).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. national stage application under 35 USC § 371of International Application No. PCT/EP2014/065337, filed on Jul. 17,2014, which claims priority to European Patent Application No.13176881.4, filed on Jul. 17, 2013, the entire contents of which areincorporated herein by reference.

The present disclosure relates to a drive mechanism for a deliverydevice, e.g. a drug delivery device such as an injector-type device anda drug delivery device.

Drug delivery devices are, for example, known from U.S. Pat. Nos.5,383,865 A, 7,699,815 B2 and WO 2006/089734 A1.

It is an object of the present disclosure to provide an alternative orimproved drive mechanism for a delivery device. Further, a drug deliverydevice should be provided.

This object is achieved by the subject-matter of the independent claims.Advantageous embodiments and refinements are subject-matter of thedependent claims.

One aspect of the present disclosure relates to a drive mechanism for adelivery device comprising a housing having a proximal end and a distalend. The drive mechanism further comprises a piston rod with a pistonrod feature. The piston rod may have a longitudinal axis. The drivemember is movable with respect to the housing, in particular in theaxial direction and/or in the radial direction. The drive membercomprises a drive feature. The drive member is further movable in theradial direction, e.g. perpendicular to the piston rod, between a firstand a second position, wherein the drive feature is selectivelyengageable with the piston rod feature by the radial displacement of thedrive member with respect to the piston rod. Preferably, thelongitudinal axis extends through the proximal end and the distal end.The proximal and the distal end may be spaced apart from each otheralong the longitudinal axis. This embodiment provides the advantagethat, depending on the engagement of drive feature and the piston rodfeature, the piston rod may be moved or displaced by a correspondingmovement of the drive member. Preferably, the piston rod and the drivemember are arranged radially next to each other.

In an embodiment, the drive mechanism is configured such that when thedrive member is in the first position, the drive member is disengagedfrom the piston rod and movable with respect to the piston rod. In thissituation, the drive member may advantageously be axially moved withrespect to the piston rod, preferably proximally for setting an amountof substance such as, e.g. a drug to be dispensed from the device anddistally for decreasing or cancelling the set amount of substance, suchthat in a later step, the drive member may be (re-)engaged to the pistonrod.

In an embodiment, the drive mechanism is configured such that, when thedrive member is in the second position, the drive feature is engagedwith the piston rod feature such that, when the drive member movesdistally with respect to the housing, said distal movement istransferred to the piston rod and the piston rod moves distally withrespect to the housing. According to this embodiment, it is achievedthat further components of the drive mechanism may effect a movement ofthe piston rod via the drive member.

A further aspect of the present disclosure relates to a drug deliverydevice comprising the drive mechanism. Preferably, the piston rod isprovisioned to advance a plunger or a piston which may be retained in acartridge of the drug delivery device in the distal direction withrespect to the cartridge such that drug which is contained in thecartridge may be dispensed from the drug delivery device. In anembodiment, the drive mechanism comprises a coupling element which isfixed to or formed integrally with the housing. The coupling elementfurther comprises a plurality of axially spaced coupling features, eachof which is configured to establish a unidirectional coupling with apiston rod feature such that a proximal movement of the piston rod withrespect to the housing is prevented. The prevention of the proximalmovement of the piston rod increases the safety of the drug deliverydevice, as the piston rod or the device is prevented from being resetand/or misused.

In an embodiment, when one of the coupling features establishes theunidirectional coupling, another one of the coupling features does notestablish the unidirectional coupling, wherein the coupling features andthe piston rod feature are configured such that the unidirectionalcoupling is formed by means of different coupling features depending onthe relative position of the piston rod and the coupling element.According to this embodiment, a movement of the piston rod with respectto the coupling element at comparably small incremental steps may becarried out, whereby the unidirectional coupling may be embodied atcomparatively large dimensions.

In an embodiment, the piston rod feature comprises a set of teeth beingarranged and configured to be engageable with the coupling features.This embodiment allows an engagement of the piston rod with the drivefeature and/or the coupling features which is dependent on the directionof relative movement. Preferably, the teeth of the piston rod areprovided along the whole or almost the whole axial length of the pistonrod. The teeth of the piston rod may be equidistantly disposed,preferably in the axial direction, along the piston rod.

In an embodiment, each of the coupling features comprises at least onetooth arranged and configured to be engageable with the teeth of thepiston rod feature. The axial space between two coupling features ischosen such that a distal end face of the tooth of a first couplingfeature abuts a proximal end face of a first tooth of the piston rodfeature. This coupling feature then establishes the unidirectionalcoupling of the piston rod with respect to the housing.

In an embodiment, the piston rod is movable by a distance which issmaller than the distance A between the proximal end faces of twoadjacent teeth of the piston rod feature.

In an embodiment, a movement of the piston rod with respect to thecoupling element is carried out at incremental steps which are smallerthan the distance A.

In an embodiment, the piston rod does not rotate.

In an embodiment, the distance D between a distal end face of the toothof a second coupling feature and a proximal end face of a second toothof the piston rod feature is smaller than the distance A between theproximal end faces of two adjacent teeth of the piston rod feature.Expediently, this embodiment facilitates a movement of the piston rodwith respect to the coupling element to be carried out at incrementalsteps which are smaller than the distance A, such that the teeth of thepiston rod may be spaced by distances greater than the minimum distanceby which the piston rod is moved. Thereby, a manufacture of said teethmay be kept cost-effective. Furthermore, particularly small amounts ofsubstance may be delivered in this way.

In an embodiment, the drive mechanism is configured such that when thepiston rod is moved distally by the distance D with respect to thehousing, the first tooth of the piston rod feature is moved out ofabutment from the tooth of the first coupling feature and the proximalend face of the second tooth of the piston rod feature abuts the distalend face of the tooth of the second coupling feature,

In an embodiment, the distance D corresponds to a minimum amount of asubstance which can be dispensed from the delivery device.

In an embodiment, the drive feature comprises a plurality of axiallyspaced drive features and each drive feature comprises at least onetooth being configured and arranged to be engageable with the teeth ofthe piston rod feature. The drive features and the piston rod featureare arranged and configured such that, when the drive member is in thesecond position, a distal end face of a tooth of one of the drivefeatures abuts a proximal end face of a tooth of the piston rod featureand a distal end face of a tooth of another drive feature is spaced bythe distance D′ from a proximal end face of a tooth of the piston rodfeature, wherein the distance D′ corresponds to the minimum amount of asubstance which can be dispensed from the delivery device. According tothe embodiment, it is assured that at least one of the drive featureseffectively abuts or engages a tooth of the piston rod feature, when thedrive member is in the second position such that the minimum amount ofthe substance can be dispensed.

In an embodiment, the drive mechanism is configured such that in asetting mode of operation, the drive member is in the first position andin a dispensing mode of operation, the drive member is in the secondposition.

In an embodiment, the drive mechanism comprises a dose member and thedrive mechanism is configured such that in a setting mode of operation,the drive member is in the first position and in a dispensing mode ofoperation, the drive member is in the second position. In the settingmode of operation, the drive member is expediently free to move axiallywith respect to the piston rod, particularly in the proximal and/ordistal direction. In the dispensing mode of operation, the drive memberexpediently transfers movement to the piston rod such that substance maybe dispensed from the delivery device.

In an embodiment, in the setting mode of operation, the dose member isrotatable in a first direction with respect to the housing to set a doseand in the dispensing mode of operation, the dose member is rotatable ina second direction opposite to the first direction with respect to thehousing to dispense a set dose.

In an embodiment the drive mechanism is configured such that therotation of the dose member with respect to the housing is convertedinto an axial movement of the drive member with respect to the pistonrod. According to this embodiment, the drive mechanism can, for example,be embodied space-saving and robust. Moreover, in this way, the drivemechanism may be embodied with a low number of interacting parts andwith a torsion spring in order to drive the piston rod. In the settingmode of operation, the drive member may be moved distally or proximally.When the set dose is increased, the drive member is, preferably, movedproximally, When the set dose is decreased, the drive member is,preferably, moved distally, In the dispensing mode of operation, thedrive member may be moved distally but preferably not moved proximally.

In an embodiment, the dose member and the drive member are threadedlycoupled with respect to each other. With this embodiment, the conversionof rotation of the dose member into an axial movement of the drivemember is achieved most expediently. Preferably, the threaded couplingbetween the dose member and the drive member is configured such that thethreaded interaction is not affected by the radial displacement thedrive member experiences with respect to the piston rod and the dosemember. To this effect, the thread coupling may comprise a certainradial play.

In an embodiment, either on the dose member or on the drive member, athreaded shaft may be provided which is elastic to a certain extent, forexample in a direction perpendicular to the longitudinal axis. Saidthreaded shaft may rotate about the longitudinal axis or an axisparallel to the longitudinal one. The dose member may comprise an outerthread which matches an inner thread of the drive member.

In an embodiment, the drive mechanism comprises a drive spring which iscoupled to the dose member. The drive spring is arranged and configuredsuch that, when the dose member rotates in a first direction withrespect to the housing, the drive spring is loaded or biased, andwherein in the dispensing mode of operation, the drive spring drives therotation of the dose member in a second direction with respect to thehousing. According to this embodiment, the drive mechanism can beembodied semi-automatic, whereby a biasing of the drive spring duringsetting, e.g. by way of a user of the drive mechanism, may provide someor all of the energy required to drive the piston rod or, as the casemay be, to dispense a substance from the delivery device. The drivespring may be a torsion spring.

In an embodiment, the drive mechanism comprises a releasable clutchmechanism, wherein the releasable clutch mechanism is configured suchthat in the setting mode of operation, the releasable clutch mechanismis engaged and the dose member is selectively rotationally locked withrespect to the housing against a spring force of the drive spring.Thereby, it is achieved that a dose can be set by the drive mechanism,as the drive spring may be locked and prevented from back-rotationand/or relaxation after a dose has been set. Preferably, when the dosemember is selectively rotationally locked with respect to the housingagainst the spring force, the dose member may still be rotated duringsetting of another dose or cancelling or decreasing of a dose by theuser. The force applied by the user in this respect may be greater thana driving force of the drive spring. The driving force may be the forceexerted by the drive spring to the piston rod.

In an embodiment, in the dispensing mode of operation, the releasableclutch mechanism is released and the dose member is rotated by the drivespring with respect to the housing. According to this embodiment, thedriving force of the drive spring may be exploited to drive the pistonrod within the cartridge and to dispense a dose of drug from the drugdelivery device.

The releasable clutch mechanism is configured to be manually operable,i.e. engagable and releasable by the user. Preferably, the clutchmechanism is configured to be engaged and/or released just by thephysical strength of the user's hand. According to this embodiment,further auxiliary means are not needed when the user operates thereleasable clutch mechanism.

In an embodiment, the drive mechanism comprises an actuation member anda displacement member, wherein the actuation member is configured tointeract with the displacement member such that when, in the settingmode of operation, an axial movement of the actuation member istransferred to a radial movement of the displacement member with respectto the piston rod, it is switched from the setting mode to thedispensing mode of operation, whereby the drive member moves from thefirst to the second position. Upon a depressing of the actuation member,the displacement member is preferably at least partly moved axially. Theactuation member may further be configured such that the user may rotateor depress the actuation member with respect to the housing in order toset or dispense a dose of drug, respectively. The actuation member maybe a dose button of the drive mechanism or the drug delivery device.

In an embodiment, the displacement member is rotationally locked withrespect to the housing and the displacement member comprises a clutchfeature wherein, in the setting mode of operation, the displacementmember is axially moved with respect to the dose member, therebyreleasing the releasable clutch mechanism. With this embodiment, thereleasable clutch mechanism can be embodied most expediently. The clutchfeature may be splined to the dose member via a tooth engagement. Tothis effect, the clutch feature may comprise a tooth or a pin and thedose member may comprise a pinion or a gear to which the tooth or pinmay be engageable. Said tooth or pin may be embodied as a protrusionprotruding from a main body of the displacement member. Alternatively,the drive mechanism may be configured such that the protrusion isprovided on the dose member.

In an embodiment, the drive mechanism comprises a guide feature which isaxially fixed to or formed integrally with the housing. The guidefeature and the displacement member are arranged and configured suchthat an axial movement of the displacement member with respect to thehousing is at least partially converted into a radial movement of thedisplacement member with respect to the piston rod, wherein thedisplacement member interacts with the drive member such that when thedisplacement member moves radially with respect to the piston rod, thedrive member is displaced with respect to the piston rod from the firstto the second position. According to this embodiment, it is simplyachieved that a radial component of movement of the displacement memberis provided without requiring further features or mechanisms of thedrive mechanism.

Features which are described herein above and below in conjunction withdifferent aspects or embodiments may also apply for other aspects andembodiments. Particularly, features described with respect to thearrangement may apply for the method, the unit and the module and viceversa.

Further features and advantages of the subject matter of this disclosurewill become apparent from the following description of the exemplaryembodiment in conjunction with the figures, in which:

FIG. 1 shows a perspective view of components of a drug delivery device.

FIGS. 2a to 2c show the schematics of a side view of components of adrive mechanism for a drug delivery device.

FIGS. 3a and 3b show a partial perspective view of components of thedrug delivery device. FIG. 3a shows a situation in which a clutchmechanism is engaged and FIG. 3b shows a situation in which the clutchmechanism is disengaged.

FIG. 4 shows a perspective view of components of the drug deliverydevice.

FIG. 5 shows a perspective view of further components of the drugdelivery device.

FIG. 6 shows a side view of components of the drug delivery device.

FIGS. 7A to 7C show the schematics of an indication mechanism of thedrug delivery device, respectively.

Like elements, elements of the same kind and identically acting elementsmay be provided with the same reference numerals in the figures.Additionally, the figures may be not true to scale. Rather, certainfeatures may be depicted in an exaggerated fashion for betterillustration of important principles.

FIG. 1 shows a perspective view of a drug delivery device 200. The drugdelivery device may be a disposable drug delivery device. The drugdelivery device 200 comprises a housing 24 which houses furthercomponents. Only one half of the housing 24 is shown in FIG. 1 such thatinner components of the drug delivery device 200 are visible. The drugdelivery device 200 further comprises a drive member 1 and a piston rod6. The piston rod may have a cross-section resembling a square,rectangle, parallelogram, circle or ellipse.

The drive member 1 is configured to move the piston rod 6 in a distaldirection, e.g. during a dose delivery of the drug delivery device 200.The drug delivery device 200 comprises a longitudinal axis x, a distalend 25 and a proximal end 26. Preferably, the longitudinal axis xextends through the distal end 25 and the proximal end 26. In otherwords, the distal end 25 and the proximal end 26 may be spaced along thelongitudinal axis. The drug delivery device 200 further comprises a,preferably replaceable, cartridge 14 in which a plunger 19 is retained.The piston rod 6 may be arranged next to or abut the plunger 19. Thecartridge 14 may further contain a drug 31 or medical substance to bedispensed from the drug delivery device 200. The drug 31 may bedispensed in measured doses. The drug 31 may be retained in thecartridge 14. The cartridge 14 may contain 1.5 ml or 3 ml of the drug31. Preferably, the cartridge 14 is arranged or aligned longitudinally.The piston rod 6 may also be arranged or retained longitudinally suchthat it is movable with respect to the cartridge 14. The drug deliverydevice 200 further comprises a dose member 2 which may effect a dosesetting and a dose dispensing of the drug delivery device. The dosemember 2 is threadedly engaged with the drive member 1, e.g. via anouter thread 22. Accordingly, the drive member 1 may comprise an innerthread matching with the outer thread 22. Thereby, said threadedengagement may be configured such that during a rotation of the dosemember 2 with respect to the housing 24, the drive member 1 is axiallymoved. In a setting mode of operation, the dose member is rotatable in afirst or second direction with respect to the housing to set a dose andin a dispensing mode of operation, the dose member 2 is rotatable in asecond direction opposite to the first direction with respect to thehousing to dispense a set dose. The drug delivery device 200 furthercomprises a displacement member 3 which may be configured to displace orto contribute to the displacement of the drive member 1.

The dose member 2 and the displacement member 3 are preferably alignedparallel to the longitudinal axis x but arranged radially offset fromthe cartridge 14 and the piston rod 6. Drive member 1 may at leastpartially be arranged between the piston rod 6 and the dose member 2. Alongitudinal axis of the drive member may thereby be aligned radially.The dose member 2 and the displacement member 3 may comprise an elongateshape, respectively. The displacement member 3 is engaged to the drivemember 1 via a guidance 27 of drive member 1. The guidance 27 may beconfigured such that, e.g., when the dose member 2 is rotated, the drivemember 1 is rotationally locked with respect to the displacement member3 such that the dose member 2 and the drive member 1 are rotatedrelative to each other. The drug delivery device 200 further comprises aspring element 4 and a dose button 5. The spring element 4 is retainedbetween a pinion 11 of the dose member 2 and the dose button 5. Thedisplacement member 3 comprises a drive member displacement member 50which comprises an elongate shape and which is aligned parallel to thelongitudinal axis x. The length of the drive member displacement member50 may relate to the travel of the drive member 1 and in this way to theamount of drug 31 to be dispensed during the dispensing of drug from thefilled cartridge. The drive member displacement member 50 is retained bythe guidance 27. Preferably, the guidance 27 rotationally and radiallylocks the drive member displacement member 50, whereby only relativeaxial movement of said components is allowed.

The displacement member 3 comprises a rod displacement feature 30. Inthe depicted situation, the drug delivery device 200 is in an initialstate. During the first use of the drug delivery device 200, the roddisplacement feature 30 may abut the piston rod 6.

The drug delivery device 200 further comprises an indication assembly100. The indication assembly 100 comprises a first indication member 110and a second indication member 120. The piston rod 6 extends through thefirst and the second indication members 110, 120. The indicationassembly 100 further comprises a locking member 130 which is configuredto rotationally lock the first and the second indication member 110, 120with respect to the housing 24. The drug delivery device 200 furthercomprises a guide feature 23 which is fixed to the housing 24. When,e.g. the dose button 5 is moved distally, the displacement member 3 isalso moved distally against the resilience of the spring element 4.Thereby, the displacement member 3 is guided by the guide feature 23which is engaged to a bore 28 of the displacement member 3. Via the bore28 and the guide feature 23, an axial movement of the displacementmember 3 may at least partly be converted into a radial movement of thedisplacement member 3 and/or the drive member displacement member 50.The displacement member 3 may comprise a certain flexibility.

The drug delivery device 200 further comprises a drive spring 13 whichis configured such that it is loaded upon a rotation of the dose member2 in a first direction (cf. arrow 29). To this effect, a distal end ofthe drive spring 13 is preferably fixed to the housing 24 and a proximalend of the drive spring 13 is preferably fixed to, e.g. a distal end ofthe dose member 2. The drive spring 13 is a torsion spring. Duringsetting of a dose of drug 31, the drive spring 13 is loaded and springenergy is stored which can be used for a delivery of the drug 31. Thedisplacement member 3 is rotationally locked with respect to the housing24. In the setting mode of operation, the dose button 5 is rotated inthe first direction 29. The dose button 5 is connected to the dosemember 2, wherein said connection is configured such that the dosemember 2 is also rotated in the first direction along with the dosebutton 5, such that the drive spring 13 is loaded. Due to the threadedengagement of the dose member 2 and the drive member 1, in the settingmode of operation, the drive member 1 is moved proximally while in thedispensing mode of operation, the drive member 1 is moved distally. Inthe setting mode of operation, the dose button 5 may also be rotated ina second direction (cf. arrow 32) opposite to the first direction 29 inorder to decrease or cancel a set dose of drug 31. This would move drivemember 1 distally. The dose button may be operated, e.g. rotated to dialthe size of a dose to be delivered. The size may span a range betweenzero units and a maximum number of gradations or units, e.g. 120.

The displacement member 3 and the dose member 2 are coupled via areleasable clutch mechanism by which said components are rotationallylockable. The releasable clutch mechanism is configured to withstand thespring force of the drive spring when a dose is set. When a maximumsettable dose is set, the releasable clutch mechanism has to withstand amaximum spring force. The releasable clutch mechanism can be released bydistal movement or depressing of the dose button 5 with respect to thehousing 24. Thereby, the displacement member 3 and the dose member 2 aredisengaged (cf. FIG. 3 further below).

The spring element 4 biases the releasable clutch mechanism towards theengaged state. In the setting mode of operation, the drive member ispreferably in a first position, wherein it is disengaged from the pistonrod 6. When the dose button 5 is depressed or moved distally which ispreferably manually performed by a user of the drug delivery device 200,it is preferably switched from the setting mode to the dispensing modeof operation. During distal movement of the dose button 5 and thedisplacement member 3 with respect to the housing 24, the displacementmember 3 is guided via the guide feature 23 in such a manner that thedisplacement member 3 displaces the drive member 1 radially, i.e.towards the piston rod 6 such that the piston rod 6 is displaced fromthe first to a second position. In the second position, the drive member1 is engaged to the piston rod 6. The drive mechanism is preferablyconfigured such that at the same time or slightly after the drive member1 has engaged the piston rod, the releasable clutch mechanism isreleased and the spring force of the loaded drive spring 13 drives thedose member 2 such that the dose member 2 is rotated in the seconddirection 32. The drive spring 13 is preferably configured to providefor a sufficient spring force for a minimum dose of drug 31 to bedispensed from the drug delivery device 200 when the piston rod 6 is inthe second position. Due to the threaded interaction of the dose member2 and the drive member 1, the drive member 1 is moved distally withrespect to the piston rod 6 when the dose member 2 rotates. The pistonrod 6 comprises a piston rod feature 17 and the drive member 1 comprisesa drive feature 15 (cf. FIG. 2). By an engagement of the drive feature15 with the piston rod feature 17, a distal movement of the drive member1 may be transferred to the piston rod 6 such that the piston rod 6 ismoved distally with respect to the housing 24. Consequently, the plunger19 is moved distally inside the cartridge 14 in order to dispense drug31 from the drug delivery device 200. The drug delivery device 200further comprises a coupling element 16 which is configured such thatthe piston rod 6 is prevented from being moved in the proximaldirection. When the dose button 5 is released either during or after adispensing operation, the releasable clutch mechanism is reengaged andthe drive member 1 is moved back from the second into the first positionthus switching the drive mechanism back into the setting mode ofoperation. The drug delivery device 200 may be an injector-type devicecomprising a needle or a needle assembly (not explicitly indicated)which may be provided at the distal end 25. Furthermore, the drugdelivery device 200 may comprise a cap (not explicitly indicated) tocover the distal end 25. The dose button 5 may need to be rotated sixtimes during setting of a dose. This may correspond to a set dose of 120units of drug 31 to be dispensed.

In the following, a priming mechanism is described by which the drugdelivery device 200 may be switched from an initial state to a primedstate. In the initial state, the drug delivery device 200 is preferablyin an as-fabricated or as-assembled state, wherein the dose button 5 hasnot yet been actuated or pressed. Then, the cartridge 14 preferablycontains an initial amount of drug 31. The rod displacement feature 30is axially movable between a first position and a second position. Inthe initial state, the piston rod 6 and the rod displacement feature 30are arranged such that some or all of the movement of the roddisplacement feature 30 from the first position to the second positionis transferred to the piston rod 6 such that the piston rod 6 is movedwith respect to the cartridge 14. In the primed state, axial movement ofthe rod displacement feature 30 from the first position to the secondposition is not transferred to the piston rod 6. Particularly, when thedose button 5 is in the initial state, a proximal face 47 of the pistonrod 6 and a distal face 46 of the rod displacement feature 30 preferablyabut (cf. also FIG. 6). Alternatively, the distance between the proximalface 47 of the piston rod 6 and a distal face 46 of the rod displacementfeature 30 is at least smaller than the distance between the first andthe second position. When, in the initial state, the dose button 5 ispressed by the user for the first time, the rod displacement member 30is moved axially, thereby moving or advancing the piston rod 6 distallywith respect to the cartridge 14. Expediently, a needle is providedwhich in turn provides fluid communication between the interior of thecartridge 14 and the outside. The dose button 5 is moved until the roddisplacement feature 30 is arranged in the second position, whereby aninitial static friction force between the plunger 19 and the cartridge14 is overcome. Thereby, the drug delivery device 200 is primed. Thepriming operation may additionally comprise the removal of clearancesand/or tolerances and the application of compression or tension tofurther device components such that the device is prepared for anoperation with no or only a minimum play between elements of the drivemechanism. The use of force transferred from the rod displacement member30 to the piston rod 6 may help the drive mechanism to overcome initialstatic friction forces, particularly between the plunger 19 and thecartridge 14.

In the primed state, the driving force is preferably sufficient to moveor advance the piston 19 distally with respect to the cartridge 14. Asan advantage, the drive spring 13 may be designed smaller and moreefficient with respect to costs and space requirements. In the initialstate, the distance between the piston rod 6 and the rod displacementfeature 30 is preferably greater than a manufacturing tolerance of thecartridge 14 and/or the piston rod 14. Thereby, it is assured, that thedirect distal movement of the rod displacement feature—which is effectedmanually by the user—is effectively transferred to the piston rod 6.Preferably, the plunger 19 and the cartridge 14 are configured such thatthe initial static friction force takes values between 10 N and 20 N.Preferably, the mentioned drive mechanism is configured such that thedriving force takes values between 3 N and 10 N.

The distance by which the dose button 5 is depressed may be 3 to 4 mm.The rod displacement feature 30 may be moved axially between the firstand the second position. The distance the rod displacement feature 30 ismoved axially may be 2 mm. Additionally, there may be a play orclearance of distance B of 1 to 2 mm between the dose button 5 and thedisplacement member 3 (cf. FIG. 6). To this effect, a further biasingmember (not explicitly indicated) may be provisioned which tends toseparate the mentioned components accordingly.

An advantage of the described priming functionality pertains to theeffect that once the drug delivery device 200 is primed, the user mayrepeat the actuation or depressing of the dose button 5 if he is notsure about the state of the device. By means of the force necessary todepress the dose button 5, the user will immediately realize whether thedevice has already been primed or not. Thereby, it is contributed to asimple and safe operation of the drug delivery device 200. The presenteddrug delivery device 200 provides the advantages of, for instance, acomfortable, user-friendly shape, a low injection force owing to thepriming mechanism, semi-automatic injection and the possibility toassemble the drug delivery device in an easy way. Moreover, the drugdelivery device may be easily distinguished from other devices due toits characteristic shape. That is to say, the shape of the drug deliverydevice may deviate slightly from a cylinder-like shape which is usualfor similar drug delivery devices. To this effect, it may be easier tohold it in the palm of the user's hand and/or to operate the drugdelivery device.

FIG. 2 illustrates a coupling between the piston rod 6 and the couplingelement 16 by means of the FIGS. 2a to 2c . Drive feature 15 of thedrive member 2 may constitute a plurality of drive features 15 which areshown each with a tilt towards the distal end 25. The depicted situationrespectively relates to the setting mode of operation, wherein the drivefeatures 15 are disengaged from the piston rod 6. The coupling element16 is preferably fixed to or integrally formed with the housing 24. Thecoupling element 16 comprises three axially spaced coupling features 20each of which comprises teeth 41. The coupling features 20 are alsotilted towards the distal end 25. The piston rod 6 comprises a set ofteeth 40 which exhibit the piston rod feature 17. The teeth 40 areconfigured uniformly and arranged equidistantly. Furthermore, the teeth40 may be arranged at an inwardly directed, as well as an outwardlydirected side surface of the piston rod 6. The side surfaces of thepiston rod 6 may be flat or non-flat, such as even. Each of the couplingfeatures 20 is configured to establish a unidirectional coupling withthe teeth 40 such that a proximal movement of the piston rod 6 withrespect to the housing 24 is prevented. In FIG. 2a , only the couplingfeature 20 b in the middle establishes said unidirectional coupling, asproximal end faces of the teeth 40 abut distal end faces of teeth 41 ofthat coupling element while this is not the case for the other couplingfeatures 20 b, c. The distance between the proximal end faces of twoadjacent teeth 40 of the piston rod 6 is indicated by A. The axialdistance between the coupling features 20 is chosen such that thedistance D between a distal end face of a tooth 41 of the couplingfeature 20 c which does not establish the unidirectional coupling and aproximal end face of a tooth 40 of the piston rod 6 feature is smallerthan the distance A. Preferably, the distance D corresponds to a minimumamount of a drug 31 to be dispensed from the delivery device 200. Thedistance D is preferably defined by those teeth 42 of the piston rod 6which are arranged proximally next to the respective tooth 41 of therespective coupling element. The distance D corresponding to a minimumamount of a drug 31 to be dispensed is expediently smaller than thedistance A. Consequently, the piston rod 6 may be moved distally withrespect to the coupling element 16 by a distance smaller than thedistance A. In FIG. 2b , as compared to the FIG. 2a , the piston rod 6has been moved distally (to the left) with respect to the couplingelement 16 by the distance D. Thereby, the proximal end faces of theteeth 40 of the piston rod 6 have been moved out of abutment with thedistal end faces of the teeth 41 of the middle coupling feature 20 b andproximal end faces of the teeth 40 abut distal end faces of the leftcoupling feature 20 a such that only this coupling feature establishesunidirectional coupling to the piston rod 6. In FIG. 2c , the piston rod6 has been moved further axially by the distance D′, as compared to FIG.2b . As a consequence, only the right coupling feature 20 c forms thementioned unidirectional coupling to the piston rod 6. The distance D′may relate to the distance D.

The drive features 15 of the drive member 1 are axially spaced, whereineach drive feature 15 comprises teeth 42 being configured to beengagable with the teeth 40 of the piston rod 6, wherein the drivefeatures 15 and the teeth 42 are configured such that when the drivemember 2 is in the second position, a distal end faces of a teeth 42 ofone of the drive features 15 abut proximal end faces of teeth 40 of thepiston rod 6 and distal end faces of a teeth 42 of another drive feature15 are spaced preferably by the distance D from proximal end faces of ateeth 40 of the piston 6.

The functionality which is described herein by means of three teeth 41may also function with coupling features and drive features which onlycomprise one tooth each. However, the provision of a plurality of teethadds greater strength and some redundancy in the case of failure.

FIG. 3a shows a partial perspective view of inner components of the drugdelivery device 200 in the setting mode of operation. The displacementmember 3 comprises a clutch feature 33 which is, in the depictedsituation, engaged to the pinion 11 of the dose member 2. In thissituation, the releasable clutch mechanism is engaged. The pinioncomprises teeth 48. The clutch feature 33 is a tooth-like clutch featurewhich is engaged or splined to the teeth 48 (cf. dashed circle).Although the dose member 2 may be selectively rotationally locked withrespect to the housing 24 against the spring force of the drive spring13, it may still be rotated, e.g. by a rotation of the dose button 5with respect to the housing 24 which is performed by the user. During asetting operation, particularly during a clockwise rotation (cf. arrow29 in FIG. 1) of the dose member 2 with respect to the displacementmember 3, said clutch interaction between the clutch feature 33 and thepinion 11 may be overcome by the user. The torque required to set a dosemay be 13.4 mNm for a set dose of zero and 25.4 mNm for a set dose of120 units. The torque required to decrease or cancel a dose may be 16.8mNm for a minimum dose and 4.8 mNm for the maximum settable dose.Expediently, said torques are larger than the torque which is applied tothe dose member 2 by the drive spring 13. FIG. 3b shows the situation inthe dispensing mode of operation, wherein the clutch feature 33 has beendisengaged from the teeth 48 of the pinion 11, by movement of the dosebutton 5 with respect to the housing 24. As compared to FIG. 3a , alsothe displacement member 3 has been moved distally with respect to thedose member 2. Consequently, in FIG. 3b , the dose member 2 is free torotate with respect to the displacement member 3. In this situation, itis enabled that the drive spring 13 drives the dose member 2 in thesecond direction or counter clockwise (cf. arrow 32 in FIG. 1) byrotation.

FIG. 4 shows parts of components of the drug delivery device 200 nearthe proximal end 26. In the setting mode of operation, the dose button 5is rotationally locked to the dose member 2 by a dose member spline 35which is retained in a recess 34 of the dose button 5 such that the dosemember 2 is rotated along with the dose button 5. In the dispensing modeof operation, the dose member 2 is free to rotate with respect to thedose button 5. To this effect, the dose member spline 35 and therecesses 34 are configured such that when the dose button 5 is moveddistally with respect to the dose member 2, e.g. during a dispensingoperation, the dose member spline 35 is disengaged from thecorresponding recess 34 and the dose member 2 is free to rotate withrespect to the dose button 5. When the dose button 5 is released again,e.g. during or after a dispensing operation, the dose member spline 35is reengaged to one of the recesses 34, e.g. to that recess which isarranged closest to the dose member spline 35. This is due to the effectof the spring element 4 which biases the dose member 2 towards thedistal end 25.

FIG. 5 shows a perspective view of components of the drug deliverydevice 200 illustrating, e.g. the function of a last dose mechanism ofthe drug delivery device 200. A last dose ratchet 37 is provisioned tohinder, e.g. a user to set a further dose when the maximum settable doseis already reached or set. When a dose of a drug 31 is set, the drivemember 1 moves away from the distal end 25. When a dose is dispensed,the piston rod 6 moves distally with respect to the housing 24 togetherwith the drive member 1. The drive member 1 comprises a drive member arm39. The last dose ratchet 37 may be borne or retained by the pins 43which may interact with a further component of the drug delivery device200 or the housing 24 such that the last dose ratchet 37 is rotatedaround an axis defined by the pins 43. The dose member 2 comprises adose member ratchet 38 further comprising teeth 44 which are disposed ona circumferential face or another face. When a large or a maximum numberof units has already been dispensed from the drug delivery device 200and/or when a large or a maximum dose is set, the drive member arm 39engages a ramp 36 near the proximal end 26. Thereby, the drive memberarm 39 is moved radially outwards, thus rotating the last dose ratchet37 around the axis which extends through the pins 43. Due to therotation of the last dose ratchet 37, an end portion 45 of the last doseratchet 37 engages the teeth 44 of the dose member ratchet 38 such thatthe dose member 2 is prevented from rotation in the first direction 29,i.e. the direction in which the set dose is increased. In the settingmode of operation, the dose member 2 may then be moved in the seconddirection (cf. arrow 32 in FIG. 1) in order to decrease or cancel thedose. Thereby, the drive member 1 is moved distally with respect to thepiston rod 6. When the maximum dose is set, the dose member 2 is thusprevented from being rotated in the first direction 29 to set anadditional dose of drug 31.

FIG. 6 shows a partial side view of inner components of the drugdelivery device 200. In the depicted situation, the drug delivery device200 is in an initial state and the rod displacement feature 30 abuts oris closely arranged to the piston rod 6. When the dose button 5 is thenmoved or depressed in the distal direction by a distance B which maycorrespond to 1 mm, the dose button abuts the displacement member 3.Upon further distal movement of the dose button 5, the displacementmember 3 and also the piston rod 6 is moved distally against theresilience of the spring element 4. The indication assembly 100 is shownin FIG. 6 in greater detail. The drug delivery device 200 may comprise awindow 21 which may be comprised by the housing 24. The dose member 2comprises a first pinion 9. The pinion 11 exhibits a second pinion, asmentioned above. The first indication member 110 further comprises afirst corresponding pinion 115 which is engaged or engagable to thefirst pinion 9. The first pinion 9 comprises a protrusion 49. The secondindication member 120 further comprises a second corresponding pinion125 which is engaged to the second pinion 11. The first and the secondindication member 110, 120 comprise indication numbers or symbols which,e.g. to indicate the size of a set dose. The first and the secondindication members 110, 120 are mechanically decoupled from one another.The dose member 2 may be suitable to drive the first and the secondindication member 110, 120, particularly to rotate said components viathe first and the second pinion 9, 11 with respect to the housing 24.The first indication member 110 may be incrementally rotatable such thatwhen the dose member 2 is rotated by one revolution, the firstindication member 110 is rotated by one increment due to an engagementof the protrusion 49 with the first corresponding pinion 115. Thelocking member 130 may be rotationally locked with respect to thehousing 24 of the drug delivery device 200. Thereby, the housing 24 maybe and/or act as a locking member guide. The first and the secondindication members 110, 120 are rotatable with respect to the lockingmember 130. The axis of rotation may be an axis parallel to thelongitudinal axis x of the drug delivery device 200. The locking member130 may be axially movable respect to the housing 24. In FIG. 6, arotation of the dose member 2 in the first direction would lead to arotation of the second indication member 120 in the second directionsuch that the number 1 would be indicated through the window 21. In FIG.7 the counting direction of the depicted numbers of the first and secondindication member 110, 120 is reversed for the sake of clarity.

By means of FIG. 7 the indication assembly 100 is describedschematically and in greater detail. The indication assembly 100 maycontribute to a display mechanism of the drug delivery device 200 whichallows, e.g. for an indication and/or counting of set doses of the drugdelivery device 200. The first indication member 110 comprises a firstindication feature 111 and the second indication member 120 comprises asecond indication feature 122 which may be a recess. The firstindication feature 111 comprises a guiding surface 112 and a stop face113. The locking member 130 comprises a first locking member feature 131and a second locking member 132. The first indication member 110 furthercomprises a cut-out 114. The first and the second locking member feature131, 132 are arranged on opposite sides of the locking member 130. Thefirst and the second indication member 110, 120 are at least partiallyarranged axially between the first and the second locking member feature131, 132.

In FIG. 7a , a dose of zero units is indicated. The locking member 130is arranged in the cut-out 114. Via the cut-out the first indicationmember 110 is rotationally locked in the second direction with respectto the locking member 130. The second indication member 120 furthercomprises a second interaction feature or stop 121. The locking member130 is arranged at an axial position, wherein it abuts the stop 121,thereby simultaneously locking the second indication member 120rotationally in the second direction with respect to the locking member130. This situation may correspond to an initial position of the lockingmember 130, wherein the set dose is zero. The first and the secondindication member 110, 120 may comprise cylindrical indication surfaces.The first and the second locking member features 131, 132 comprise oneor more even surfaces which are arranged obliquely with respect to theaxis of rotation of the first or the second indication member 110, 120.The first and the second indication member 110, 120 may rotate around acommon axis, preferably around the longitudinal axis x. When a dose ofthe drug delivery device 200 is set, the dose member 2 is rotated in thefirst direction via the dose button 5 such that this set dose may beindicated through the window 21. Such rotation may relate to a rotationof the first and the second indication member 110, 120 in a firstrotational direction with respect to the locking member 130. A rotationof the dose member 2 in the second direction relates, accordingly, to arotation of the first and the second indication member 110, 120 in asecond rotational direction with respect to the locking member 130. Whena dose of the drug delivery device 200 is set, the second pinion 11,drives the second corresponding pinion 125 of the second indicationmember 120 such that the set dose, i.e. the dose indicated by theindication assembly 100 increases. Thus, when, in FIG. 7, the indicateddose (which may correspond to the number in the middle) is increased,the indication assembly 100 and the dose member 2 are configured suchthat, when the second indication member 120 is rotated for onerevolution, the first indication member 110 is rotated by an anglecorresponding to one digit such that “1” is indicated instead of “0”.Thereby, the locking member 130 is moved axially and out of the cut-out114 of the first indication member 110. Now the locking member 130 is ina non-locking position, as, for example, shown in FIG. 7c by means ofthe indicated dose of 51 units. The locking member 130 is biased towardssaid non-locking position by a biasing member (not explicitly indicated)with respect to the first and the second indication members 110, 120.Preferably, the locking member is biased towards the initial position ofthe locking member 130. When the maximum dose of, for example 120 units,is set (cf. FIG. 7b ), which may correspond to a predetermined angle ofthe first and/or the second indication member 110, 120 with respect tothe locking member 130, the first locking member feature 131 interactswith the first interaction feature 111 such that the locking member 130is displaced into a locking position (cf. FIG. 7b ) with respect to theindication member 130, thereby rotationally locking the first and thesecond indication member 110, 120 with respect to the locking member 130in the first direction. The displacement of the locking member 130 withrespect to the first and the second indication member 110, 120 is anaxial displacement, e.g. along the longitudinal axis x of the drugdelivery device 200 (cf. FIG. 1). In the second direction, the first andthe second indication member 110, 120 are still rotatable with respectto the locking member 130. The rotation in the second direction mayrelate to an operation of the drug delivery device 200, wherein a doseis decreased or cancelled. The axial displacement of the locking member130 is guided by the guiding surface 112 such that the second lockingmember feature 132 is axially displaced into the second indicationfeature 122. In FIG. 7b , the locking member 130 abuts the stop face113. Now, the first and the second indication member 110, 120 arerotationally locked in the first direction with respect to the lockingmember 130. This situation may relate to an indication of the maximumsettable dose (cf. “120” in FIG. 7b ).

As an advantage of the presented indication assembly, a display orindication mechanism for the drug delivery device can be provided whichfunctions with a low number mutually interacting components and thus thecounting assembly can be embodied robust and safe.

An application of the presented indication assembly is not restricted todrug delivery device, but merely illustrated exemplarily by that means.

The end of a dose delivery action may be indicated by a feature (notexplicitly indicated) which provides an audible feedback when furthercomponents of the drug delivery device move relative to one another.

The drug delivery device may additionally comprise components which arenot explicitly indicated and/or the function of which is not describedherein. For instance, the presented device may comprise a mechanismwhich decouples or ratchets the dose button relative to the dose memberif an excessive torque is applied to the dose button by the user in thesetting mode of operation.

Although this is not explicitly described herein, the actuation memberand the displacement member may be embodied in a single component andthe whole configuration of the drive mechanism and/or the device may beadjusted accordingly.

A further variant of the design may allow the user to decouple thecoupling feature from the piston rod feature such that the piston rodcan be moved axially, e.g. proximally, with respect to the housing. Thisis particularly advantageous when the drug delivery device is configuredreusable such that the piston rod can be reset and the cartridge can bechanged.

The drive mechanism may further comprise a clutch element which isconfigured to receive motion of the actuation member when the userattempts to set a dose greater than the maximum settable dose. This maybe embodied by means of a torque limiter comprising, e.g. protrusions,recesses and/or resilient elements preventing destruction or damage ofcomponents of the drive mechanism and/or the drug delivery device whenthe user attempts to set a dose greater than the maximum settable dose.

The term “drug” or “substance”, as used herein, preferably means apharmaceutical formulation containing at least one pharmaceuticallyactive compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a protein, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivatives are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N—(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(02)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropin (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropin (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycan, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, δ, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystallizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H—H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

The scope of protection of the invention is not limited to the examplesgiven hereinabove. The invention is embodied in each novelcharacteristic and each combination of characteristics, whichparticularly includes every combination of any features which are statedin the claims, even if this feature or this combination of features isnot explicitly stated in the claims or in the examples.

REFERENCE NUMERALS

-   1 Drive member-   2 Dose member-   3 Displacement member-   4 Spring element-   5 Dose button-   6 Piston rod-   9 First pinion-   11 Second pinion-   13 Drive spring-   14 Cartridge-   15 Drive feature-   16 Coupling element-   17 Piston rod feature-   19 Plunger-   20 Coupling feature-   21 Window-   22 Outer thread-   23 Guide feature-   24 Housing-   25 Distal end-   26 Proximal end-   27 Guidance-   28 Bore-   29 First direction-   30 Rod displacement feature-   31 Drug-   32 Second direction-   33 Clutch feature-   34 Recess (dose button)-   35 Dose member spline-   36 Ramp-   37 Last dose ratchet-   38 Dose member ratchet-   39 Drive member arm-   40 Teeth (piston rod)-   41 Teeth (coupling element)-   42 Teeth (drive feature)-   43 Pin-   44 Teeth (dose member ratchet)-   45 End portion-   46 Distal face-   47 Proximal face-   48 Teeth (second pinion)-   49 Protrusion-   50 Drive member displacement member-   100 Indication assembly-   110 First indication member-   111 First interaction feature-   112 Guiding surface-   113 Stop face-   114 Cut-out-   115 First corresponding pinion-   120 Second indication member-   121 Second interaction feature-   122 Second indication feature/recess-   125 Second corresponding pinion-   130 Locking member-   131 First locking member feature-   132 Second locking member feature-   200 Drug delivery device-   x Longitudinal axis-   A,B,D Distance

The invention claimed is:
 1. A drive mechanism for a delivery device,the drive mechanism comprising: a housing having a proximal end and adistal end; a piston rod having a longitudinal axis and a piston rodfeature; a drive member movable with respect to the housing, the drivemember comprising a drive feature, the drive member radially movablebetween a first position and a second position, wherein the drivefeature is selectively engageable with the piston rod feature by aradial displacement of the drive member with respect to the piston rod,the drive mechanism configured such that: when the drive member is inthe first position, the drive member is disengaged from the piston rodand movable with respect to the piston rod, and when the drive member isin the second position, the drive feature is engaged with the piston rodfeature such that, when the drive member moves distally with respect tothe housing, a distal movement of the drive member with respect to thehousing is transferred to the piston rod such that the piston rod movesdistally with respect to the housing; and a coupling element fixed to orformed integrally with the housing, the coupling element comprising aplurality of axially spaced coupling features each of which isconfigured to establish a unidirectional coupling with the piston rodfeature such that a proximal movement of the piston rod with respect tothe housing is prevented, wherein when one of the coupling featuresestablishes the unidirectional coupling, another one of the couplingfeatures does not establish the unidirectional coupling and wherein thecoupling features and the piston rod feature are configured such thatthe unidirectional coupling is formed by different coupling featuresdepending on a relative position of the piston rod and the couplingelement.
 2. The drive mechanism according to claim 1, wherein the pistonrod feature comprises a set of teeth arranged and configured to beengageable with the coupling features.
 3. The drive mechanism accordingto claim 2, wherein each of the coupling features comprises at least onetooth arranged and configured to be engageable with the set of teeth ofthe piston rod feature and wherein an axial distance between thecoupling features is chosen such that a distal end face of the at leastone tooth of a first coupling feature of the coupling features abuts aproximal end face of a first tooth of the set of teeth of the piston rodfeature and a distance D between a distal end face of the at least onetooth of a second coupling feature of the coupling features and aproximal end face of a second tooth of the set of teeth of the pistonrod feature is smaller than a distance A between the proximal end facesof two adjacent teeth of the set of teeth of the piston rod feature. 4.The drive mechanism according to claim 3, wherein the drive mechanism isconfigured such that, when the piston rod is moved distally by thedistance D with respect to the housing, the first tooth of the pistonrod feature is moved out of abutment with the at least one tooth of thefirst coupling feature and the proximal end face of the second tooth ofthe piston rod feature abuts the distal end face of the at least onetooth of the second coupling feature, wherein the distance D correspondsto a minimum amount of substance which can be dispensed from thedelivery device.
 5. The drive mechanism according to claim 1, whereinthe drive feature comprises a plurality of axially spaced drive featuresand each drive feature comprises at least one tooth configured andarranged to be engageable with a set of teeth of the piston rod feature,wherein the drive features and the piston rod feature are arranged andconfigured such that when the drive member is in the second position, adistal end face of the at least one tooth of one of the drive featuresabuts a proximal end face of a tooth of the piston rod feature and adistal end face of the at least one tooth of another one of the drivefeatures is spaced by a distance D′ from a proximal end face of anothertooth of the piston rod feature, wherein the distance D′ corresponds toa minimum amount of substance which can be dispensed from the deliverydevice.
 6. The drive mechanism according to claim 1, comprising a dosemember, wherein the drive mechanism is configured such that in a settingmode of operation, the drive member is in the first position and in adispensing mode of operation, the drive member is in the secondposition, wherein in the setting mode of operation, the dose member isrotatable in a first direction with respect to the housing to set a doseand in the dispensing mode of operation, the dose member is rotatable ina second direction opposite to the first direction with respect to thehousing to dispense a set dose.
 7. The drive mechanism according toclaim 6, wherein the drive mechanism is configured such that a rotationof the dose member with respect to the housing is converted into anaxial movement of the drive member with respect to the piston rod. 8.The drive mechanism according to claim 6, wherein the dose member andthe drive member are threadedly coupled to each other.
 9. The drivemechanism according to claim 6, comprising a drive spring which iscoupled to the dose member, the drive spring arranged and configuredsuch that, when the dose member rotates in the first direction withrespect to the housing, the drive spring is loaded and wherein in thedispensing mode of operation, the drive spring drives a rotation of thedose member in the second direction with respect to the housing.
 10. Thedrive mechanism according to claim 9, comprising a releasable clutchmechanism, wherein the releasable clutch mechanism is configured suchthat, in the setting mode of operation, the releasable clutch mechanismis engaged and the dose member is selectively rotationally locked withrespect to the housing against a spring force of the drive spring and,in the dispensing mode of operation, the releasable clutch mechanism isreleased and the dose member is rotated by the drive spring with respectto the housing.
 11. The drive mechanism according to claim 6, comprisingan actuation member and a displacement member, wherein the actuationmember is configured to interact with the displacement member such that,when in the setting mode of operation, an axial movement of theactuation member is transferred to a radial movement of the displacementmember with respect to the piston rod, the drive mechanism is switchedfrom the setting mode of operation to the dispensing mode of operation,whereby the drive member moves from the first position to the secondposition.
 12. The drive mechanism according to claim 11, comprising aguide feature which is axially fixed to or formed integrally with thehousing, wherein the guide feature and the displacement member arearranged and configured such that an axial movement of the displacementmember with respect to the housing is at least partially converted intoa radial movement of the displacement member with respect to the pistonrod, wherein the displacement member interacts with the drive membersuch that, when the displacement member moves radially with respect tothe piston rod, the drive member is displaced with respect to the pistonrod from the first position to the second position.
 13. The drivemechanism according to claim 10, wherein a displacement member isrotationally locked with respect to the housing and the displacementmember comprises a clutch feature which is part of the releasable clutchmechanism, wherein in the setting mode of operation, the displacementmember is axially moved with respect to the dose member, therebyreleasing the releasable clutch mechanism.
 14. Drug A drug deliverydevice comprising: a drive mechanism comprising: a housing having aproximal end and a distal end; a piston rod having a longitudinal axis(x) and a piston rod feature; a drive member movable with respect to thehousing, the drive member comprising a drive feature, the drive memberradially movable between a first and a second position, wherein thedrive feature is selectively engageable with the piston rod feature by aradial displacement of the drive member with respect to the piston rod,the drive mechanism configured such that: when the drive member is inthe first position, the drive member is disengaged from the piston rodand movable with respect to the piston rod, and when the drive member isin the second position, the drive feature is engaged with the piston rodfeature such that, when the drive member moves distally with respect tothe housing, a distal movement of the drive member with respect to thehousing is transferred to the piston rod such that the piston rod movesdistally with respect to the housing; and a coupling element fixed to orformed integrally with the housing, the coupling element comprising aplurality of axially spaced coupling features each of which isconfigured to establish a unidirectional coupling with the piston rodfeature such that a proximal movement of the piston rod with respect tothe housing is prevented, wherein when one of the coupling featuresestablishes the unidirectional coupling, another one of the couplingfeatures does not establish the unidirectional coupling and wherein thecoupling features and the piston rod feature are configured such thatthe unidirectional coupling is formed by different coupling featuresdepending on a relative position of the piston rod and the couplingelement.
 15. A drive mechanism for a delivery device, the drivemechanism comprising: a housing having a proximal end and a distal end;a piston rod having a longitudinal axis and a piston rod feature; and adrive member movable with respect to the housing, the drive membercomprising a drive feature, the drive member radially movable between afirst position and a second position, wherein the drive feature isselectively engageable with the piston rod feature by a radialdisplacement of the drive member with respect to the piston rod, thedrive mechanism configured such that: when the drive member is in thefirst position, the drive member is disengaged from the piston rod andmovable with respect to the piston rod, and when the drive member is inthe second position, the drive feature is engaged with the piston rodfeature such that, when the drive member moves distally with respect tothe housing, a distal movement of the drive member with respect to thehousing is transferred to the piston rod such that the piston rod movesdistally with respect to the housing, wherein the drive featurecomprises a plurality of axially spaced drive features and each drivefeature comprises at least one tooth configured and arranged to beengageable with a set of teeth of the piston rod feature, wherein thedrive features and the piston rod feature are arranged and configuredsuch that when the drive member is in the second position, a distal endface of the at least one tooth of one of the drive features abuts aproximal end face of a tooth of the piston rod feature and a distal endface of the at least one tooth of another one of the drive features isspaced by a distance D′ from a proximal end face of another tooth of thepiston rod feature, wherein the distance D′ corresponds to a minimumamount of substance which can be dispensed from the delivery device.